Sequential IL-23 and IL-17 and increased Mmp8 and Mmp14 expression characterize the progression of an experimental model of periodontal disease in type 1 diabetes

J Cell Physiol. 2012 Jun;227(6):2441-50. doi: 10.1002/jcp.22979.

Abstract

Molecular mechanisms responsible for periodontal disease (PD) and its worsening in type 1 Diabetes Mellitus (DM1) remain unknown. Cytokine profile and expression levels of collagenases, Mmp14, and tissue inhibitors were determined, as were the numbers of neutrophils and macrophages in combined streptozotocin-induced DM1 and ligature-induced PD models. Increased IL-23 (80-fold) and Mmp8 expression (25-fold) was found in DM1. Ligature resulted in an IL-1β/IL-6 profile, increased expression of Mmp8, Mmp13, and Mmp14 (but not Mmp1), and transient expression of Timp1 and Reck in non-diabetics. PD in DM1 involved IL-1β (but not IL-6) and IL-23/IL-17, reduced IL-6 and IL-10, sustained Mmp8 and Mmp14, increased Mmp13 and reduced Reck expression in association with 20-fold higher counts of neutrophils and macrophages. IL-23 and Mmp8 expression are hallmarks of DM1. In association with the IL-1/IL-6 (Th1) response in PD, one found a secondary IL-17 (Th17) pathway in non-diabetic rats. Low IL-6/TNF-α suggest that the Th1 response was compromised in DM1, while IL-17 indicates a prevalence of the Th17 pathway, resulting in high neutrophil recruitment. Mmp8, Mmp13, and Mmp14 expression seems important in the tissue destruction during PD in DM1. PD-associated IL-1/IL-6 (Th1), IL-10, and Reck expression are associated with the acute-to-chronic inflammation transition, which is lost in DM1. In conclusion, IL-23/IL-17 are associated with the PD progression in DM1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alveolar Bone Loss / enzymology
  • Alveolar Bone Loss / etiology
  • Alveolar Bone Loss / immunology
  • Animals
  • Diabetes Mellitus, Experimental / complications*
  • Diabetes Mellitus, Experimental / enzymology
  • Diabetes Mellitus, Experimental / genetics
  • Diabetes Mellitus, Experimental / immunology
  • Diabetes Mellitus, Type 1 / complications*
  • Diabetes Mellitus, Type 1 / enzymology
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology
  • Disease Progression
  • GPI-Linked Proteins / metabolism
  • Gingiva / enzymology*
  • Gingiva / immunology*
  • Inflammation Mediators / metabolism*
  • Interleukin-10 / metabolism
  • Interleukin-17 / metabolism*
  • Interleukin-1beta / metabolism
  • Interleukin-23 / metabolism*
  • Interleukin-6 / metabolism
  • Ligation
  • Macrophages / immunology
  • Male
  • Matrix Metalloproteinase 13 / metabolism
  • Matrix Metalloproteinase 14 / genetics
  • Matrix Metalloproteinase 14 / metabolism*
  • Matrix Metalloproteinase 8 / genetics
  • Matrix Metalloproteinase 8 / metabolism*
  • Molar / surgery
  • Neutrophil Infiltration
  • Neutrophils / immunology
  • Periodontal Diseases / complications*
  • Periodontal Diseases / enzymology
  • Periodontal Diseases / genetics
  • Periodontal Diseases / immunology
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Th17 Cells / immunology
  • Time Factors
  • Tumor Suppressor Proteins / metabolism
  • Up-Regulation

Substances

  • GPI-Linked Proteins
  • Il17a protein, rat
  • Inflammation Mediators
  • Interleukin-17
  • Interleukin-1beta
  • Interleukin-23
  • Interleukin-6
  • RNA, Messenger
  • Reck protein, rat
  • Tumor Suppressor Proteins
  • Interleukin-10
  • Matrix Metalloproteinase 13
  • Mmp13 protein, rat
  • Matrix Metalloproteinase 8
  • Matrix Metalloproteinase 14